The European Medicines Agency (EMA) plans on publishing a series of guidance documents to assist applicants in the medical device industry in preparation of the obligations delivered by the new Regulation (EU) 2017/745 on medical devices. This guidance document falls within the scope of EMA’s activities and should be read in alignment with the new Regulations (EU) 2017/745 on medical devices and (EU) 2017/746 on In Vitro Diagnostic medical devices.
Both Regulations have extended the number of roles and responsibilities for EMA and National Competent Authorities (NCAs) pertaining to specific types of medical devices and In-Vitro Diagnostic medical devices. With the rapidly increasing pace of technology development, it comes without a surprise that the EMA has inherited new responsibilities in regulating complex medical devices that have a medicinal component. The objective of the Agency is to work in collaboration with the EU Regulatory network, stakeholders from both the pharmaceutical and medical device industries, as well as the Notified Bodies, to establish a smooth transition to the new regulatory framework.
The first questions and answers (Q&A) document, developed by the EMA in a joint effort with the Co-ordination Group for Mutual Recognition and Decentralized Procedures – Human (CMDH), and in close partnership with the European Commission, focuses on Article 117 of the Regulation (EU) 2017/745 on medical devices . The document states that marketing authorization applications for medicinal products with an integral medical device shall include opinion from a Notified Body. It is approximated that one in four centrally authorized medications often includes a medical device component.
The guidance document addresses questions and provides answers on items such as:
1. When is a medicinal product considered to form an integral product with the administration device?
- A medicinal product is considered to form an integral product with the administration device if all the following conditions are met: the device and the medicinal product form a single integral product, they are intended exclusively for use in the given combination, and are not reusable. Examples: pre-filled pens, pre-filled syringes, pre-filled inhalers etc.
2. How will the medical devices Regulation and in particular Article 117 impact new marketing authorization applications?
- NON CE marked device: Marketing authorization applications that pertain to a medicinal product with an integral medical device submitted by May 26, 2020 must demonstrate that the medical devices meets the necessary requirements of Annex I of Regulation (EU) 2017/745. In addition, an opinion from a notified body must be provided for the medical device component.
- CE marked device: Marketing authorization applications that pertain to a medicinal product with an integral medical device submitted by May 26, 2020 must demonstrate that the medical devices meets the necessary requirements of Annex I of Regulation (EU) 2017/745. In addition, a declaration of conformity and EU notified body certificate need to be provided for the medical device component. If the necessary documentation is unavailable, then an opinion form a notified body must be obtained for the medical device component.
3. When is it required to provide the notified body opinion/EU certificate/declaration of conformity with my Marketing Authorization Application (MAA)?
- Article 117 only applies to marketing authorization applications submitted by May 26, 2020. It will not apply to applications submitted before the given date.
4. At what stage do I need to submit the Notified Body opinion?
- The EMA and national competent authorities (NCAs) highly recommend that medical device manufacturers submit the EU certificate or notified body opinion as part of the dossier of the initial marketing authorization application for a medicinal product to help facilitate a seamless and smooth running of the procedure.
5. How does Article 117 of the medical devices regulation impact currently authorized medicinal products with an integral medical device?
- Article 117 is not intended to be imposed on medicinal products with an integral medical device that has already been authorized including MAAs that have been submitted prior to May 26th, 2020. However, if there is substantial change after authorization to the design or intended purpose of the medical device, or perhaps there is a completely new device introduced then all required documentation (certificate, declaration of conformity, NB opinion) must be submitted as part of the variation/extension application, as applicable to EMA/NCA
6. Will I need to provide a (new or updated) EU certificate / declaration of conformity / notified body opinion if there are changes to the device submitted through a variation / extension?
- There are two cases in which a new or updated version of the above mentioned documentation is needed. The first case is when an addition of full replacement of the medical device component is added for application submitted as of May 26th, 2020. The second case is when there have been substantial design changes to the medical device component. Changes to the device component are considered to be substantial if the changes affect the safety characteristics and performance of the device. If the variation does not affect the medical device then a certificate of a new/updated notified body opinion is not required. Lastly giving the short timelines for variation procedures, it is best to submit the documentation to support the CE mark or the notified body opinion to avoid delays.
The EMA will publish further updates to their questions and answers document in order to address additional requirements for different categories of medical devices with: substances that are systemically absorbed, products which are not clearly defined as medicinal products, borderline products, and in vitro diagnostic tests used to determine patients’ eligibility for a specific medical treatment.